The malfunctioning of protein kinases (PKs) is the hallmark of numerous diseases. A large share of the oncogenes and proto-oncogenes involved in human cancers code for PKs. The enhanced activities of PKs are also implicated in many non-malignant diseases, such as benign prostate hyperplasia, familial adenomatosis, polyposis, neuro-fibromatosis, psoriasis, vascular smooth cell proliferation associated with atherosclerosis, pulmonary fibrosis, arthritis glomerulonephritis and post-surgical stenosis and restenosis. PKs are also implicated in inflammatory conditions and in the multiplication of viruses and parasites. PKs can also play a major role in the pathogenesis and development of neurodegenerative disorders. PKs malfunctioning and disregulation are further discussed in Current Opinion in Chemical Biology 1999, 3, 459-465.
Among the several protein kinases known in the art as being implicated in the growth of cancer cells is Cdc7, an evolutionary conserved serine-threonine kinase which plays a pivotal role in linking cell cycle regulation to genome duplication, being essential for the firing of DNA replication origins (see Montagnoli A. et al., EMBO Journal, Vol. 21, No. 12, pp. 3171-3181, 2002; Montagnoli A. et al., Cancer Research Vol. 64, October 1, pp. 7110-7116, 2004).
Blache, et al. in Heterocycles (2000), 53(4), 905-916, describe a regioselective synthesis of polyfused indolones, in particular there is disclosed a compound named 7H-pyrido[4,3-a]carbazol-7-one, 8,9,10,11-tetrahydro-11-(phenylmethyl).
Several heterocyclic compounds are known in the art as protein kinase inhibitors. Among them are, for instance, pyridinylpyrroles disclosed in WO 2005/13986, pyrimidinylpyrroles disclosed in WO 2005/14572, pyrrolo-pyrazoles disclosed in WO 02/12242; tetrahydroindazoles disclosed in WO 00/69846; pyrrolo-pyridines disclosed in WO 01/98299; aminophthalazinones disclosed in WO 03/014090 and aminoindazoles disclosed in WO 03/028720.
Beta-carbolines and analogs for use as mitogen-activated protein kinase-activated protein kinase-2 inhibitors, such as 7H-pyrido[3′,4′:4,5]pyrrolo[2,3-f]isoquinolin-7-one, 8,9,10,11-tetrahydro, are described and claimed in WO 2005/009370.
In addition, pyrrolopyridinone derivatives for the treatment of obesity are disclosed in the patent WO03/027114 to Bayer Pharmaceuticals Corporation. In particular a pyridylpyrrolopyridinone, namely 5-cyclohexyl-1-(2,4-dichloro-phenyl)-3-methyl-2-pyridin-3-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one is reported.
Pyrrolopyridinone derivatives, endowed with mitogen activated protein kinase-activated protein kinase-2 inhibitory activity, are disclosed in the patent application WO2004/058762 A1 to Pharmacia Corp.